Project Summary/Abstract Increases in cancer incidence and rising cancer costs highlight the need to advance cancer biology through the growth of a well-trained workforce. City of Hope, an NCI-designated Comprehensive Cancer Center, is known internationally for clinical cancer research and has an outstanding record of research in the basic sciences, with an emphasis on cancer research. Therefore, this proposed program, supported by the robust cancer research environment at City of Hope, is dedicated to training young scientists in a setting that will prepare them to become leaders in cancer research. Almost all human cancers have alterations in signaling pathways associated with DNA damage response and oncogenic signaling (DDROS). Therefore, to develop the next generation of cancer researchers, a multidisciplinary, institution-wide cancer biology training program is proposed to train postdoctoral fellows in DDROS. The 3 T32-supported postdoctoral trainees supported for up to 3 years will be selected for the DDROS program through a rigorous process, including a personal interview. Annual reappointment will be based on annual written reports, mentor reports, and presentations. Each trainee will establish a mentoring committee that will include a physician to favor the cross-pollination of ideas between the basic and translational aspects of cancer research. As part of an incentive to the DDROS program, City of Hope will provide an additional postdoctoral trainee position for every underrepresented minority trainee recruited, up to a total of 6 positions. Furthermore, to attract the best postdoctoral candidates at a national level, City of Hope will commit to salary supplementation for all DDROS trainees, a stipend for research supplies, and full administrative and faculty salary support. In this highly collaborative environment, trainees will have the opportunity to participate in multidisciplinary research that seeks to translate innovative basic research findings into powerful methods for preventing or treating cancer. Trainees will be mentored by 18 faculty members, all of whom are performing cancer-focused, funded, high-impact research in DDROS and have a history of mentoring postdoctoral fellows. To enhance their chances of securing academic positions, all DDROS trainees will take a unique common curriculum that provides a continuum of learning including scientific coursework, professional development, and the ethical conduct of research. In addition, trainees will participate in cutting-edge research programs, journal clubs, data clubs, seminars, symposiums, monthly luncheons with mentors, workshops, national and international scientific conferences, and finally a yearly DDROS Symposium. The stellar 29 Shared Resource Facilities associated with the Cancer Center will also provide training in state-of the art technologies. The request for funding of this research training grant is justified by the relevance of the research training to cancer, the exceptional environment for the overlap of basic and translational cancer research, the superb experience of the mentors in training, the outstanding commitment of City of Hope, and the diverse population of the geographical area served by our institution.